Trulance safe, effective for treatment of chronic idiopathic constipation in adults
Trulance safely and significantly improved constipation and related symptoms in adults with chronic idiopathic constipation, according to the results of a phase 3 randomized controlled trial.
The FDA recently approved Trulance (plecanatide, Synergy Pharmaceuticals) for the treatment of chronic idiopathic constipation (CIC) in adults, and it will be available in the U.S. this quarter, according to a press release from the manufacturer. It is an orally administered compound designed to replicate the function of the human GI peptide uroguanylin to stimulate fluid secretion and promote stool consistency.
“There are millions of CIC patients in the U.S., many of whom suffer with symptoms that remain untreated or fail to respond to current treatments,” Satish S.C. Rao, MD, PhD, professor of medicine and director of neurogastroenterology and motility at the Digestive Health Center at Augusta University, said in the press release. “Trulance has demonstrated efficacy with a low rate of adverse events, such as diarrhea, providing health care providers and their patients with an additional, much needed, new treatment option.”
In this multicenter trial, investigators randomly assigned 1,394 CIC patients from 164 centers in the U.S. and Canada to receive placebo or 3 mg or 6 mg of plecanatide once daily for 12 weeks between December 2013 and April 2015. Patients recorded daily bowel movements, stool consistency and abdominal symptoms in an electronic diary, and the proportion of patients who were durable overall complete spontaneous bowel movement (CSBM) responders served as the primary endpoint.
“An overall CSBM responder was a patient who was a weekly CSBM responder for at least 9 of the 12 treatment weeks, and a durable overall CSBM responder was also a weekly responder in at least 3 of the last 4 weeks,” the investigators wrote.
Overall, 21% of the 3-mg group and 19.5% of the 6-mg group achieved the primary endpoint compared with 10.2% of the placebo group (P < .001 for both).
Moreover, CSBM frequency increased from baseline by a mean of 2.5 per week in the 3-mg group and 2.2 per week in the 6-mg group compared with 1.2 per week in the placebo group (P < .001 for both). Similarly, spontaneous bowel movement frequency increased by a mean of 3.2 per week in the 3-mg group and 3.1 per week in the 6-mg group compared with 1.3 per week in the placebo group (P < .001 for both).
Both doses of the study drug also significantly improved secondary endpoints vs. placebo such as stool consistency, straining, abdominal bloating and discomfort, and health-related quality of life.
Diarrhea was the most common adverse event, was mostly mild to moderate in severity, and occurred in 5.9% of the 3-mg group, 5.7% of the 6-mg group and 1.3% of the placebo group.
The investigators concluded that plecanatide “appears to be a promising new treatment for patients with CIC.”
The manufacturer has also reported positive results from two phase 3 clinical trials of plecanatide in constipation-predominant irritable bowel syndrome, and will file a supplemental new drug application this quarter, according to the press release. – by Adam Leitenberger
Disclosures: Synergy Pharmaceuticals funded this trial. Rao reports he serves on the advisory committee/board and consults for Forest Laboratories. Several other researchers report financial relationships with Synergy Pharmaceuticals.